Alleviation of Neuropathic Pain Hypersensitivity by Inhibiting Neuronal Pentraxin 1 in the Rostral Ventromedial Medulla

作者：Zapata Agustin^*; Pontis Silvia; Schepers Raf J; Wang Ruizhong; Oh Eric; Stein Alexandra; Baeckman Cristina M; Worley Paul; Enguita Marta; Alba Abad M; Trullas Ramon; Shippenberg Toni S

来源：Journal of Neuroscience, 2012, 32(36): 12431-12436.

DOI：10.1523/JNEUROSCI.2730-12.2012

Peripheral nerve injury causes spontaneous and long-lasting pain, hyperalgesia, and allodynia. Excitatory amino acid receptor-dependent increases in descending facilitatory drive from the brainstem rostral ventromedial medulla (RVM) contribute to injury-evoked hypersensitivity. Although increased excitability likely reflects changes in synaptic efficacy, the cellular mechanisms underlying injury-induced synaptic plasticity are poorly understood. Neuronal pentraxin 1 (NP1), a protein with exclusive CNS expression, is implicated in synaptogenesis and AMPA receptor recruitment to immature synapses. Its role in the adult brain and in descending pain facilitation is unknown. Here, we use the spared nerve injury (SNI) model in rodents to examine this issue. We show that SNI increases RVMNP1 expression and constitutive deletion or silencing NP1 in the RVM, before or after SNI, attenuates allodynia and hyperalgesia in rats. Selective rescue of RVM NP1 expression restores behavioral hypersensitivity of knock-out mice, demonstrating a key role of RVM NP1 in the pathogenesis of neuropathic pain.

• 出版日期2012-9-5